An animal may experience immunological stress for a number of reasons, including exposure to an antigen that is recognized by the animal's immune system. An antigen may trigger an immune response that is an adaptive immune response or that is an innate immune response. When an immune response is triggered, the animal experiences immunological stress as its immune system responds to the perceived threat. Often, immunological stress hampers animal growth performance.
Acute phase proteins (APP) are a group of blood proteins whose blood concentration changes when an animal is experiencing stress, such as infection, inflammation, surgical trauma, or other internal or external challenges. See, e.g., Murata et al., Vet. J. 168: 28 (2004). APP are believed to play a role in an animal's innate immune response. For example, APP may be involved in restoring homeostasis and restraining microbial growth until an acquired immunity is developed.
APP include “negative” proteins whose concentration decreases with stress, and “positive” proteins whose concentration increases with stress. See, e.g., Murata et al., supra. Negative APP include albumin and transferrin. Positive APP include proteins synthesized by hepatocytes upon stimulation by pro-inflammatory cytokines and released into the bloodstream, such as haptoglobin, C-reactive protein, serum amyloid A, ceruloplasmin, fibrinogen, and α-1-acid glycoprotein (AGP). Extra-hepatic production of APP also has been reported for most mammalian species. Id. Pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) are believed to be the major mediators of APP synthesis in the liver. Inflammation, infection or tissue injury triggers cytokine release by defense-oriented cells, thereby inducing APP synthesis. The induction of positive APP also is associated with a decrease in the synthesis of negative APP. Id.
Methods of quantifying APP have been established, and circulating APP concentration (e.g., serum levels of APP) has been correlated to the severity of the animal's condition. Id. Thus, APP concentration can be used as an indicator of an animal's immune stress level.
An animal's immune system may recognize antigens that do not pose a real threat to the animal's health, such as plant- and animal-derived ingredients in animal feed compositions. These antigens may trigger an immune response, such as an innate immune response, thereby causing the animal to experience immunological stress. This stress response can be identified and monitored via serum APP concentration.
Even when the immune-triggering antigen did not pose a real threat to the animal's health, the stress response can have a detrimental effect. This may be observed as a decrease in feed efficiency, a decrease in weight gain rate or decrease in weight, an increase in susceptibility to infection, or an increase in body temperature, for example.
The use of antibodies, such as anti-phospholipase A2 antibodies, to reduce gastrointestinal inflammation in animals has been described. See, e.g., U.S. Pat. No. 6,383,485. Feed compositions have been described that comprise a hemicellulase capable of degrading β-mannan-containing hemicellulose (e.g., a β-mannanase-type hemicellulase), such as endo-1,4-β-mannanase, or a phospholipase, such as phospholipase A2, for improved feed efficiency. See, e.g., WO 97/41739, U.S. Pat. No. 6,162,473, and U.S. Pat. No. 6,183,739.
Likewise described have been feed compositions comprised of an enzyme, such as PI-PLC, that cleaves a linkage, thereby to effect release of a cell-surface protein or carbohydrate, for the treatment or prevention of digestive tract infection. See, e.g., WO 01/41785. Walsh et al., J. Anim. Sci. 73: 1074 (1995), discuss feed compositions comprising glucanase enzymes that cleave a mixed link glucan substrate, such as 1,4-β-glucanase which cleaves mixed β-1,3, β-1,4-substrates. In our tests, however, neither PI-PLC nor 1,4-β-glucanase displayed immune-stress reducing activity.
There has been no description heretofore of a feed composition comprised of an enzyme that is other than a β-mannanase-type hemicellulase or a phospholipase and that is present in an amount effective to reduce immunological stress.
Accordingly, there is a need for compositions and methodology for reducing immunological stress in animals.